Cefis 2024 Acta Physiol (Oxf)

From Bioblast
Publications in the MiPMap
Cefis M, Dargegen M, Marcangeli V, Taherkhani S, Dulac M, Leduc-Gaudet JP, Mayaki D, Hussain SNA, Gouspillou G (2024) MFN2 overexpression in skeletal muscles of young and old mice causes a mild hypertrophy without altering mitochondrial respiration and H2O2 emission. Acta Physiol (Oxf) [Epub ahead of print]. https://doi.org/10.1111/apha.14119

Β» PMID: 38400630 Open Access

Cefis Marina, Dargegen Manon, Marcangeli Vincent, Taherkhani Shima, Dulac Maude, Leduc-Gaudet Jean-Philippe, Mayaki Dominique, Hussain Sabah NA, Gouspillou Gilles (2024) Acta Physiol (Oxf)

Abstract: Sarcopenia, the aging-related loss of muscle mass and function, is a debilitating process negatively impacting the quality of life of affected individuals. Although the mechanisms underlying sarcopenia are incompletely understood, impairments in mitochondrial dynamics, including mitochondrial fusion, have been proposed as a contributing factor. However, the potential of upregulating mitochondrial fusion proteins to alleviate the effects of aging on skeletal muscles remains unexplored. We therefore hypothesized that overexpressing Mitofusin 2 (MFN2) in skeletal muscle in vivo would mitigate the effects of aging on muscle mass and improve mitochondrial function.

MFN2 was overexpressed in young (7 mo) and old (24 mo) male mice for 4 months through intramuscular injections of an adeno-associated viruses. The impacts of MFN2 overexpression on muscle mass and fiber size (histology), mitochondrial respiration, and H2O2 emission (Oroboros fluororespirometry), and various signaling pathways (qPCR and western blotting) were investigated.

MFN2 overexpression increased muscle mass and fiber size in both young and old mice. No sign of fibrosis, necrosis, or inflammation was found upon MFN2 overexpression, indicating that the hypertrophy triggered by MFN2 overexpression was not pathological. MFN2 overexpression even reduced the proportion of fibers with central nuclei in old muscles. Importantly, MFN2 overexpression had no impact on muscle mitochondrial respiration and H2O2 emission in both young and old mice. MFN2 overexpression attenuated the increase in markers of impaired autophagy in old muscles.

MFN2 overexpression may be a viable approach to mitigate aging-related muscle atrophy and may have applications for other muscle disorders. β€’ Keywords: Autophagy, Mitochondria, Mitochondrial dynamics, Mitochondrial fusion, Mitofusin 2, Sarcopenia, Skeletal muscle aging β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: CA Montreal Gouspillou G

Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style  Pathology: Aging;senescence 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS  Pathway: N, NS, ROX  HRR: Oxygraph-2k, O2k-Fluorometer 

2024-02, AmR 

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